Protective effects of α-mangostin against acetaminophen-induced acute liver injury in mice

The purpose of this study was to evaluate the protective effects of alpha-mangostin against acetaminophen (APAP)induced acute liver injury and discover its potential mechanisms in mice. Mice were continuously treated with alpha-mangostin (12.5 and 25 mg/kg) by intragastric administration once daily for 6 days, and injected intraperitoneally with APAP (300 mg/kg) after 1 h of alpha-mangostin administration on the last day. After APAP exposure for 24 h, the liver and serum were gathered to evaluate the hepatotoxicity. The results showed that alpha-mangostin effectively decreased the serum levels of alanine aminotransferase, aspartate transaminase, tumor necrosis factor (TNF-alpha), interleukin-1 beta and 6 (IL-1 beta, IL-6), and hepatic malondialdehyde level; and recovered hepatic glutathione (GSH), superoxide dismutase and catalase activities. Liver histopathological observation provided further evidence that alpha-mangostin pretreatment significantly inhibited APAP-induced hepatocellular necrosis, infiltration of inflammatory cell and hyperemia. According to the analysis of western-blot and RT-PCR detection, alpha-mangostin pretreatment validly inhibited the phosphorylation of ERK, JNK and p38 MAPK induced by APAP, which was consistent with the changes of TNF-alpha, IL-6 and IL-1 beta levels; the phosphorylation of I kappa B alpha and the translocation of NF-kappa Bp65 were also attenuated by alpha-mangostin. These results provided a new mechanism for the protective effects of alpha-mangostin against APAP-induced acute liver injury. alpha-Mangostin significantly restrainted the oxidative stress induced by APAP. Moreover, the anti-inflammatory property of alpha-mangostin, which is mediated by the NF-kappa B and MAPK signaling pathways, also contributed to its hepatoprotective effect. Taken together, we believed that alpha-mangostin might be a potential material for drug development against drug-related hepatotoxicity.